title: Endosomal trafficking of the ligated FcvarepsilonRI receptor.
abstract: In addition to initiating signaling cascades leading to mast cell mediator release, aggregation of the high affinity IgE receptor (FcvarepsilonRI) leads to rapid internalization of the cross-linked receptor. However, little is known about the trafficking of the internalized FcvarepsilonRI. Here we demonstrate that in RBL-2H3 cells, aggregated FcvarepsilonRI appears in the early endosomal antigen 1 (EEA1(+)) domains of the early endosomes within 15min after ligation. Minimal co-localization of FcvarepsilonRI with Rab5 was observed by 30min, followed by its appearance in the Rab7(+) late endosomes and lysosomes at later time points. During endosomal sorting, FcvarepsilonRIalpha and gamma subunits remain associated. In Syk-deficient RBL-2H3 cells, the rate of transport to lysosomes is markedly increased. Taken together, our data demonstrate time-dependent sorting of aggregated FcvarepsilonRI within the endosomal-lysosomal network, and that Syk may play an essential role in regulating the trafficking and retention of FcvarepsilonRI in endosomes.
authors.affiliation: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, United States.
authors.forename: Gul'nar V
authors.initials: GV
authors.lastname: Fattakhova
authors.forename: Madhan
authors.initials: M
authors.lastname: Masilamani
authors.forename: Sriram
authors.initials: S
authors.lastname: Narayanan
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrego
authors.forename: Alasdair M
authors.initials: AM
authors.lastname: Gilfillan
authors.forename: Dean D
authors.initials: DD
authors.lastname: Metcalfe
authors.forename: John E
authors.initials: JE
authors.lastname: Coligan
mesh_terms: D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000235:genetics / Q000276:immunology*; D007152:Immunologic Capping / Q000235:genetics / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology; D008247:Lysosomes / Q000235:genetics / Q000276:immunology*; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology; D051381:Rats; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology*; D000072377:Syk Kinase; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000276:immunology; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D000090802:rab7 GTP-Binding Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D000090802:rab7 GTP-Binding Proteins; C000716466:rab7 GTP-binding proteins, rat; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; D020691:rab GTP-Binding Proteins